EU-Beitrag:

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MC-ERG - European Re-integration Grants (ERG)

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Regenerative therapies involving stem cells are now beginning to realise their potential. Their use for bone marrow transplantation is already a reality and their potential for the treatment of other degenerative diseases is being studied in clinical trials throughout the world. One of the challenges in stem cell therapy is the possibility to monitor the fate of stem cells once they are transplanted to a patient. This is of relevance given the need of stem cells to localise at the target tissue only, as their migration to other parts of the body can lead to adverse consequences. In this project, we aim at developing the technology which is necessary for long-term stem cell tracking. This will be based on the use of magnetic resonance imaging (MRI) in combination with contrast agents based on superparamagnetic iron oxide nanoparticles (SPION). Although contrast agents based on SPION are commercially available, none offer the potential for long-term tracking of stem-cells. This limitation is based on the observations that after a few weeks, these contrast agents are not retained by stem cells anymore. Additionally, the SPION tend to be slowly degraded in the cells, limiting the time frame in which they can be used. As potential adverse effects caused by stem cells would likely arise in a time scale of months or years, the need for monitoring them for such periods is of importance. Here, we aim at developing new SPION with multifunctional surface properties that will address these limitations. SPION will be designed and synthesised in order to exhibit targeting moieties that allow their internalisation and long-term retention within stem cells. The developed SPION will be evaluated in vitro in order to assess their cytotoxicity, internalisation dynamics and retention. Nanoparticles which are shown to be suitable for long-term tracking via MRI in vitro will be finally studied in vivo by monitoring bone marrow stem cells implanted in mice displaying a renal injury.